A total of seventeen combretastatin compounds have been isolated from the South African bushwillow tree Combretum caffrum by Pettit and co-workers. Among these seventeen compounds, Combretastatin A4 (CA4) (1) has emerged as the most potent anti-cancer agent. CA4 is a vascular disruptive agent which inhibits tubulin polymerization. CA4 can induce cancer cell cytotoxicity in the low nanomolar range and is also active against multidrug resistant cancer cells. The cis-isomer of CA4 is the biologically active form, but it is known to easily isomerize to its inactive trans-geometrical isomer.
In order to stabilize the active geometrical cis-isomeric form of CA4, various cis-constricted combretastatin analogs have been previously synthesized and tested for their anticancer activity. However, in this respect, 4,5-disubstituted-2H-1,2,3-triazoles have received little attention, probably because of the difficulty in preparing them.
In the current work, we have developed a simple and novel synthetic procedure for the synthesis of cis-geometrically configured 4,5-disubstituted-2H-1,2,4-triazoles as analogs of CA4. The synthesized 4,5-disubstituted-2H,1,2,3-triazoles have been evaluated for their anticancer activity and are found to be potent cytotoxic agents.